Is CTSE p.Arg23Trp (c.67A>T) pathogenic?

CTSE p.Arg23Trp (c.67A>T) is classified Uncertain significance in CTSE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: ambiguous (0.3746); Rare (popmax 0.151%, afr).

How common is CTSE p.Arg23Trp (c.67A>T) in the general population?

CTSE p.Arg23Trp (c.67A>T) is rare (popmax 0.151%, afr) (gnomAD).

What do computational predictors say about CTSE p.Arg23Trp (c.67A>T)?

AlphaMissense predicts ambiguous (score 0.3746) — an in-silico prediction, not a clinical call.

CTSE p.Arg23Trp

c.67A>T · rs143511888 · VCV3078760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3746 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, afr)

Computational evidence

Protein change
AlphaMissense	0.3746	ambiguous
SaProt	LLR -14.70	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.41	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.8	GERP 0.47, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 14 kb · p 0.083 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.151% African / African-American · 113/75,026 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.00756% 122/1,613,474 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.151%	664
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.00333%	30,003

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CTSE
Protein: p.Arg23Trp
Coding: c.67A>T
MANE Select: NM_001910
dbSNP: rs143511888
Type: single nucleotide variant
Location: chr1:206023725 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.31 · 1 PDB
Residue 23: a β-strand

Full CTSE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTSE p.Arg23Ser Uncertain significance ★ ⚠ same residue
CTSE p.Gly80Asp Uncertain significance ★★ ⚠ same type
CTSE p.Ala206Thr Uncertain significance ★ ⚠ same type
CTSE p.Ala259Pro Uncertain significance ★ ⚠ same type
CTSE p.Arg28Ser Uncertain significance ★ ⚠ same type
CTSE p.Arg37Gln Uncertain significance ★ ⚠ same type
CTSE p.Arg37Trp Uncertain significance ★ ⚠ same type
CTSE p.Arg384Cys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ctse-p-arg23trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown